12 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

pharmacogenomics

These pubmed results were generated on 2020/03/21

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Impaired bile secretion promotes hepatobiliary injury in Sickle Cell Disease.

Hepatology. 2020 Mar 19;:

Authors: Vats R, Liu S, Zhu J, Mukhi D, Tutuncuoglu E, Cardenes N, Singh S, Brzoska T, Kosar K, Bamne M, Jonassaint J, Adebayo Michael A, Watkins SC, Hillery C, Ma X, Nejak-Bowen K, Rojas M, Gladwin MT, Kato GJ, Ramakrishnan S, Sundd P, Pal Monga S, Pradhan-Sundd T

Abstract
Hepatic crisis is an emergent complication affecting sickle cell disease (SCD) patients, however, the molecular mechanism of sickle cell hepatobiliary injury remains poorly understood. Using the knock-in humanized mouse model of SCD and SCD patient blood, we sought to mechanistically characterize SCD-associated hepato-pathophysiology applying our recently developed quantitative liver intravital imaging, RNA sequence analysis, and biochemical approaches. SCD mice manifested sinusoidal ischemia, progressive hepatomegaly, liver injury, hyperbilirubinemia, and increased ductular reaction under basal conditions. NF-κB activation in the liver of SCD mice inhibited FXR signaling and its downstream targets, leading to loss of canallicular bile transport and altered bile acid pool. Intravital imaging revealed impaired bile secretion into the bile canaliculi, which was secondary to loss of canallicular bile transport and bile acid metabolism, leading to intrahepatic bile accumulation in SCD mice liver. Blocking NF-κB activation rescued FXR-signaling, and partially ameliorated liver injury and sinusoidal ischemia in SCD mice. These findings are the first to identify that NF-κB-FXR dependent impaired bile secretion promotes intrahepatic bile accumulation, which contributes to hepatobiliary injury of SCD. Improved understanding of these processes could potentially benefit the development of new therapies to treat sickle cell hepatic crisis.

PMID: 32190913 [PubMed - as supplied by publisher]

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C9 and Nonsteroidal Anti-inflammatory Drugs.

Clin Pharmacol Ther. 2020 Mar 19;:

Authors: Theken KN, Lee CR, Gong L, Caudle KE, Formea CM, Gaedigk A, Klein TE, Agúndez JAG, Grosser T

Abstract
Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used analgesics due to their lack of addictive potential. However, NSAIDs have the potential to cause serious gastrointestinal, renal, and cardiovascular adverse events. CYP2C9 polymorphisms influence metabolism and clearance of several drugs in this class, thereby affecting drug exposure and potentially safety. We summarize evidence from the published literature supporting these associations and provide therapeutic recommendations for NSAIDs based on CYP2C9 genotype (updates at www.cpicpgx.org).

PMID: 32189324 [PubMed - as supplied by publisher]

15 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

pharmacogenomics

These pubmed results were generated on 2020/03/19

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

14 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

pharmacogenomics

These pubmed results were generated on 2020/03/19

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

A Multi-Omics Approach to Liver Diseases: Integration of Single Nuclei Transcriptomics with Proteomics and HiCap Bulk Data in Human Liver.

OMICS. 2020 Mar 16;:

Authors: Cavalli M, Diamanti K, Pan G, Spalinskas R, Kumar C, Deshmukh AS, Mann M, Sahlén P, Komorowski J, Wadelius C

Abstract
The liver is the largest solid organ and a primary metabolic hub. In recent years, intact cell nuclei were used to perform single-nuclei RNA-seq (snRNA-seq) for tissues difficult to dissociate and for flash-frozen archived tissue samples to discover unknown and rare cell subpopulations. In this study, we performed snRNA-seq of a liver sample to identify subpopulations of cells based on nuclear transcriptomics. In 4282 single nuclei, we detected, on average, 1377 active genes and we identified seven major cell types. We integrated data from 94,286 distal interactions (p < 0.05) for 7682 promoters from a targeted chromosome conformation capture technique (HiCap) and mass spectrometry proteomics for the same liver sample. We observed a reasonable correlation between proteomics and in silico bulk snRNA-seq (r = 0.47) using tissue-independent gene-specific protein abundancy estimation factors. We specifically looked at genes of medical importance. The DPYD gene is involved in the pharmacogenetics of fluoropyrimidine toxicity and some of its variants are analyzed for clinical purposes. We identified a new putative polymorphic regulatory element, which may contribute to variation in toxicity. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and we investigated all known risk genes. We identified a complex regulatory landscape for the SLC2A2 gene with 16 candidate enhancers. Three of them harbor somatic motif breaking and other mutations in HCC in the Pan Cancer Analysis of Whole Genomes dataset and are candidates to contribute to malignancy. Our results highlight the potential of a multi-omics approach in the study of human diseases.

PMID: 32181701 [PubMed - as supplied by publisher]

Genetic Diversity of HLA Class I and Class II Alleles in Thai Populations: Contribution to Genotype-Guided Therapeutics.

Front Pharmacol. 2020;11:78

Authors: Satapornpong P, Jinda P, Jantararoungtong T, Koomdee N, Chaichan C, Pratoomwun J, Na Nakorn C, Aekplakorn W, Wilantho A, Ngamphiw C, Tongsima S, Sukasem C

Abstract
Human leukocyte antigen (HLA) class I and II are known to have association with severe cutaneous adverse reactions (SCARs) when exposing to certain drug treatment. Due to genetic differences at population level, drug hypersensitivity reactions are varied, and thus common pharmacogenetics markers for one country might be different from another country, for instance, HLA-A*31:01 is associated with carbamazepine (CBZ)-induced SCARs in European and Japanese while HLA-B*15:02 is associated with CBZ-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) among Taiwanese and Southeast Asian. Such differences pose a major challenge to prevent drug hypersensitivity when pharmacogenetics cannot be ubiquitously and efficiently translated into clinic. Therefore, a population-wide study of the distribution of HLA-pharmacogenetics markers is needed. This work presents a study of Thai HLA alleles on both HLA class I and II genes from 470 unrelated Thai individuals by means of polymerase chain reaction sequence-specific oligonucleotide (PCR-SSO) in which oligonucleotide probes along the stretches of HLA-A, -B, -C, -DRB1, -DQA1, and -DQB1 genes were genotyped. These 470 individuals were selected according to their regional locations, which were from North, Northeast, South, Central, and a capital city, Bangkok. Top ranked HLA alleles in Thai population include HLA-A*11:01 (26.06%), -B*46:01 (14.04%), -C* 01:02 (17.13%), -DRB1*12:02 (15.32%), -DQA1*01:01 (24.89%), and -DQB1*05:02 (21.28%). The results revealed that the distribution of HLA-pharmacogenetics alleles from the South had more HLA-B75 family that a typical HLA-B*15:02 pharmacogenetics test for SJS/TEN screening would not cover. Besides the view across the nation, when compared HLA alleles from Thai population with HLA alleles from both European and Asian countries, the distribution landscape of HLA-associated drug hypersensitivity across many countries could be observed. Consequently, this pharmacogenetics database offers a comprehensive view of pharmacogenetics marker distribution in Thailand that could be used as a reference for other Southeast Asian countries to validate the feasibility of their future pharmacogenetics deployment.

PMID: 32180714 [PubMed]

Fibrate pharmacogenomics: expanding past the genome.

Pharmacogenomics. 2020 Mar 17;:

Authors: House JS, Motsinger-Reif AA

Abstract
Fibrates are a medication class prescribed for decades as 'broad-spectrum' lipid-modifying agents used to lower blood triglyceride levels and raise high-density lipoprotein cholesterol levels. Such lipid changes are associated with a decrease in cardiovascular disease, and fibrates are commonly used to reduce risk of dangerous cardiovascular outcomes. As with most drugs, it is well established that response to fibrate treatment is variable, and this variation is heritable. This has motivated the investigation of pharmacogenomic determinants of response, and multiple studies have discovered a number of genes associated with fibrate response. Similar to other complex traits, the interrogation of single nucleotide polymorphisms using candidate gene or genome-wide approaches has not revealed a substantial portion of response variation. However, recent innovations in technological platforms and advances in statistical methodologies are revolutionizing the use and integration of other 'omes' in pharmacogenomics studies. Here, we detail successes, challenges, and recent advances in fibrate pharmacogenomics.

PMID: 32180510 [PubMed - as supplied by publisher]

Are pharmacists from the province of Quebec ready to integrate pharmacogenetics into their practice.

Pharmacogenomics. 2020 Mar 17;:

Authors: Petit C, Croisetière A, Chen F, Laverdière I

Abstract
Aim: The pharmacists are identified as one of the best positioned health professionals to lead intercollaborative efforts in tailoring medication based on pharmacogenetic information. As pharmacotherapy specialists, they can take on a prominent role in ordering and interpreting pharmacogenetic test results and then guiding optimal drug selection and dose based on those results. Participants & methods: To assess the readiness of pharmacists and trainees in the province of Quebec to assume this role, we surveyed their knowledge in (pharmaco)genetics, their confidence in their ability to use pharmacogenetics and their attitude toward the integration of this tool in clinical practice. Results: A total of 99 pharmacists (community: 67.7%, hospital: 24.2% and other: 8.1%) and 36 students volunteered in a self-administered online survey. About 50% of the questions on the participants' knowledge are answered correctly, with a stepwise increase of right answers with hours of education in (pharmaco)genetics (51.2, 63.8 and 76.7% for <5, 5-25 and >25 h respectively; p < 0.0001). While the majority of participants believe that pharmacogenetics will gain more room in their future practice (80.7%), the overall rate of confidence in their ability to use pharmacogenetics information is low (22%) and 90.3% desire more training. Conclusion: The limited experience of pharmacists in pharmacogenetics appears to be a barrier for its integration in clinical practice.

PMID: 32180495 [PubMed - as supplied by publisher]

Is HLA-B*58:01 genotyping cost effective in guiding allopurinol use in gout patients with chronic kidney disease?

Pharmacogenomics. 2020 Mar 17;:

Authors: Teng GG, Tan-Koi WC, Dong D, Sung C

Abstract
Aim: Concerns for fatal severe cutaneous adverse reactions (SCARs) hamper allopurinol use. Methods and material: We adopted a health system perspective to evaluate the cost-effectiveness of HLA-B*58:01 genotyping before allopurinol initiation. A decision tree compared three treatment strategies in gout patients with chronic kidney disease who have higher risk for SCAR. They were standard allopurinol treatment followed by febuxostat in nonresponders, test-positive patients receive febuxostat while test-negative receive allopurinol and universal use of febuxostat. Results: The first strategy was the most cost effective. Genotyping dominated universal febuxostat use. Time horizon and SCAR incidence were the most influential factors on the incremental cost-effectiveness ratio. Conclusion: HLA-B*58:01 genotyping compared with standard allopurinol-febuxostat sequential treatment does not provide good value for money in gout with chronic kidney disease.

PMID: 32180492 [PubMed - as supplied by publisher]

Higher Optimization of Pharmacokinetic and Pharmacodynamic Parameters Through Loading Dose of Intravenous Colistin in Pediatric Patients.

Int J Antimicrob Agents. 2020 Mar 13;:105940

Authors: Wacharachaisurapol N, Phasomsap C, Sukkummee W, Phaisal W, Chanakul A, Wittayalertpanya S, Chariyavilaskul P, Puthanakit T

Abstract
BACKGROUND: Colistin use in children is rising in accordance with the surge of multidrug-resistant Gram-negative bacteria (MDR-GNB). In adults, colistin loading dose is recommended to achieve the therapeutic level within 12-24 hours. We aimed to describe pharmacokinetic (PK) parameters of a loading dose versus a recommended initial dose of intravenous colistimethate sodium (CMS) in pediatric patients.
METHODS: A prospective, open-label, PK study was conducted in pediatric patients aged 2 - 18 years with normal renal function. Patients were randomly assigned to receive either CMS loading dose (LD group) of 4 mg of colistin base activity (CBA)/kg/dose or standard initial dose (NLD group) of 2.5 mg (12-h interval) or 1.7 mg (8-h interval) of CBA/kg/dose. Serial blood samples were collected. Plasma concentration of formed colistin was measured by LC-MS/MS method. PK parameters were reported. Acute kidney injury (AKI) was monitored by serum creatinine and urine NGAL.
RESULTS: Twenty children were enrolled. The median (interquartile range) age and body weight were 8.5 years (3.5-11.3) and 21.5 kg (13.5-20.0). The mean (standard deviation) of first-dose PK parameters of the LD group vs the NLD group were Cmax 6.1 (2.4) vs 4.1 (1.3) mg/L, AUC0-t 26.5 (12.5) vs 13.5 (3.6) mg/L*h, Vd 0.7 (0.4) vs 0.6 (0.3) L/kg, and t1/2 2.9 (0.6) vs 2.6 (0.4) h. There was no patient developed AKI by serum creatinine criteria.
CONCLUSIONS: CMS loading dose is beneficial for the improvement of colistin exposure without increased AKI. A higher daily dose of CMS should be considered especially for MDR-GNB treatment.

PMID: 32179149 [PubMed - as supplied by publisher]

Mapping the Mutation Landscape of Colorectal Cancer.

Am J Med Sci. 2019 11;358(5):313-314

Authors: Newsom KJ, Starostik P

PMID: 31655711 [PubMed - indexed for MEDLINE]

20 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

pharmacogenomics

These pubmed results were generated on 2020/03/17

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

19 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

pharmacogenomics

These pubmed results were generated on 2020/03/17

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Genotype-guided warfarin therapy: Still of only questionable value two decades on.

J Clin Pharm Ther. 2020 Mar 13;:

Authors: Shah RR

Abstract
WHAT IS KNOWN AND OBJECTIVE: Despite an apparently sound pharmacological basis, clinical studies of genotype-guided warfarin dosing have yielded mixed and conflicting results, leading to reluctance in its clinical implementation. The objective of this critique is to re-evaluate key warfarin pharmacogenetic studies with a view to explaining why this may be so.
METHODS: Major widely-cited warfarin pharmacogenetic studies as well as recent meta-analyses were identified and a critical analysis of these was undertaken to identify factors that may account for poor clinical implementation of pre-treatment genotyping.
RESULTS AND DISCUSSION: Critical examination of major warfarin pharmacogenetic studies identified a number of methodological concerns such as marked variations in study designs with different variously-defined measures of outcome. Genotype testing involved only a limited number of CYP2C9/VKORC1 alleles. Claims of benefits of genotyping are based almost exclusively on INR-related parameters which are known to be highly time-labile and of limited value in predicting clinical risk or benefit. This is evidenced by lack of any significant effect of genotyping on rates of bleeding or thromboembolic events. Neither have the effects of potential phenoconversion or medication non-adherence in study populations been adequately investigated. Although the effect of ethnicity/race is now better characterised, studies lack the power to determine whether any benefits claimed are indication-sensitive.
WHAT IS NEW AND CONCLUSION: Since 60% of inter-individual variability in warfarin dose/response is due to other factors (many of which are non-genetic), expectations of eliminating this variability simply by CYP2C9/VKORC1 genotyping are over-optimistic and efforts cost-ineffective. Real-world studies have not always corroborated trials-based claims of clinical benefit. It is time to consider redirecting scarce resources away from the study of warfarin pharmacogenetics to pharmacogenetic research of potentially greater clinical relevance.

PMID: 32168383 [PubMed - as supplied by publisher]

Primary care prescription drug use and related actionable drug-gene interactions in the Danish population.

Clin Transl Sci. 2020 Mar 12;:

Authors: Lunenburg CATC, Sebastian Hauser A, Ishtiak-Ahmed K, Gasse C

Abstract
Pharmacogenetics (PGx) aims to improve drug therapy using the individual patients' genetic make-up. Little is known about the potential impact of PGx on the population level, possibly hindering implementation of PGx in clinical care. Therefore, we investigated how many patients use actionable PGx drugs, have actionable geno- or phenotypes and which patients could benefit the most of PGx testing. We included PGx recommendations from two international PGx consortia (CPIC and DPWG). Using data from public Danish prescription registries (MEDSTAT), we identified the number of users of actionable prescription PGx drugs among the total Danish population in 2017. We estimated actionable geno- or phenotypes based on reported frequencies from literature. We identified 49 drug-gene interactions (DGIs) related to 41 unique prescription drugs. The estimated median frequency of actionable geno- or phenotypes among prescription drug users was 25% (interquartile range: 7-26%). Six out of 41 drugs were used more than twice as much in females. Actionable PGx drugs were most frequently used by 45-79 years olds (62%), followed by 25-44 year olds (18%). Almost half of the actionable PGx drugs (19/41) were psychotropics, i.e. antidepressants, antipsychotics or psychostimulants. PGx testing can have a substantial impact on the population, as one in four prescription drug users has an actionable geno- or phenotype and could thus benefit from PGx testing. We advocate for prospective panel-based PGx testing at the time of the first PGx drug prescription ('as needed'), with PGx results ready prior to start of the first, and all future, therapies.

PMID: 32166845 [PubMed - as supplied by publisher]

Explaining Heart Failure Hyper-mortality in Sub Saharan Africa: Global Genomic and Environmental Contribution Review.

J Natl Med Assoc. 2020 Mar 09;:

Authors: Ajayi AA, Sofowora GG, Ladipo GO

Abstract
The annual heart failure (HF) mortality rate in Africa is 34% according to the INTERHF study. This is twice the world average of 16.5% and 3.7 times that of South America, 9%. We review evidence-based explanations for the Hyper-mortality of HF, by comparison of North American, Caribbean, Afro-Brazilian with Sub-Saharan African (SSA) nations profiles, and suggest amelioration. 1 year HF mortality rates in SSA ranged from 29% to 58%, and intra-hospital mortality rate from 8 to 26% (n = 8). A clustering of adverse genetic single nucleotide polymorphisms (SNP) predisposing to hypertension and/or left ventricular hypertrophy (LVH) in the black diaspora may contribute. A higher prevalence of HF with reduced Ejection Fraction (HF r EF) phenotype, which is associated with greater mortality is more common in SSA nations. Additionally, a worse co-morbidity burden, especially valvular regurgitations causing LV remodeling (LVR), chronic kidney disease (CKD), anemia, lung disease, infections, late presentation in NYHA III/IV, right ventricular disease (RVD) were also common in SSA. Geographic variation in SSA, HF risk factors and co-morbidity was observed. There was sub-optimal use of guideline directed medical therapy (GDMT) and intracardiac device (ICD) unavailability. Gross Domestic Product -per purchasing power parity (GDP-PPP), which is low in SSA, was inversely correlated both to higher intra-hospital mortality rate % (r = -0.73, r 2 = 0.54 p = 0.038) and higher 1 year HF mortality rate % (r = -0.62, r 2 = 0.38, = 0.098). Localized primary prevention, early detection and prompt treatment of hypertension, diabetes, rheumatic fever, early cardiac valve repair and use of cardiovascular polypill, optimal use of GDMT, national health insurance scheme are advocated to stem the dismal mortality and cost burden of HF.

PMID: 32165009 [PubMed - as supplied by publisher]

A Hereditable Mutation of MSH2 Gene Associated with Lynch Syndrome in a Five Generation Chinese Family.

Cancer Manag Res. 2020;12:1469-1482

Authors: Shao WH, Wang CY, Wang LY, Xiao F, Xiao DS, Yang H, Long XY, Zhang L, Luo HG, Yin JY, Wu W

Abstract
Purpose: In order to clarify which variants of the MMR gene could provide current "healthy" members in affected families a more accurate risk assessment or predictive testing.
Patients and Methods: One family, which meets the criteria according to both Amsterdam I/II and Bethesda guidelines, is reported in this study. The proband and some relatives of the patient have been investigated for whole genome sequencing, microsatellite instability, immunohistochemical MMR protein staining and verified by Sanger sequencing.
Results: A heterozygous insertion of uncertain significance (c.420dup, p.Met141Tyrfs) in MSH2 gene was found in proband (III-16) and part of His relatives. The variant was associated with a lack of expression of MSH2 protein (MMR deficient) and high microsatellite instability analysis (MSI) status in tumor tissues of LS patients. In addition, we found that the variant could affect the expression of MSH2 and the response to chemotherapy drugs in vitro.
Conclusion: We identified an insertion mutation (rs1114167810, c.420dup, p.Met141Tyrfs) in MSH2 in LS using whole genome-wide sequencing (WGS). We further confirmed that this mutation plays an important role in LS patients of this pedigree based on in vivo and vitro study.

PMID: 32161499 [PubMed]

A population pharmacokinetic model for escitalopram and its major metabolite in depressive patients during the perinatal period: prediction of infant drug exposure through breast milk.

Br J Clin Pharmacol. 2020 Mar 12;:

Authors: Weisskopf E, Guidi M, Fischer CJ, Bickle Graz M, Beaufils E, Nguyen KA, Morisod Harari M, Rouiller S, Rothenburger S, Gaucherand P, Kassai-Koupai B, Borradori Tolsa C, Epiney M, Tolsa JF, Vial Y, Hascoët JM, Claris O, Eap CB, Panchaud A, Csajka C

Abstract
BACKGROUND AND OBJECTIVES: Escitalopram (SCIT) is frequently prescribed to breastfeeding women. Available information on SCIT excretion into breast milk is based on heterogeneous and incomplete data. A population pharmacokinetic model aiming to better characterize maternal and infant exposure to SCIT and its metabolite was developed.
METHODS: The study population was composed of women treated by SCIT or racemic citalopram and enrolled in the multicenter prospective cohort study SSRI-Breast Milk study (ClinicalTrial.gov NCT01796132). A joint structural model was first built for SCIT and S-desmethylcitalopram (SDCIT) in plasma using NONMEM® and the milk-to-plasma ratios (MPR) was estimated by adding the drug breast milk concentrations. The effect of different influential covariates was tested and the average drug exposure with variability through breastfeeding was predicted under various conditions by simulation.
RESULTS: The study enrolled 33 patients treated with SCIT or racemic citalopram who provided 80 blood and 104 milk samples. Mean MPR for both parent drug and metabolite was 1.9. Increased milk fat content was significantly associated with an increased drug transfer into breast milk (+28% for SCIT and +18% for SDCIT when fat amount doubles from 3.1 to 6.2 g/100 ml). Simulations suggested that an exclusively breastfed infant would ingest daily through breast milk 3.3% of the weight-adjusted maternal SCIT dose on average.
CONCLUSION: The moderate between-subject variability in milk concentration of SCIT and the limited exposure to escitalopram through breast milk observed provide reassurance for treated mothers of breastfed healthy infants.

PMID: 32162723 [PubMed - as supplied by publisher]

Phenylethanolamine N-methyltransferase gene polymorphisms associate with crisis pain in sickle cell disease patients.

Pharmacogenomics. 2020 Mar 12;:

Authors: Sadhu N, Jhun EH, Posen A, Yao Y, He Y, Molokie RE, Wilkie DJ, Wang ZJ

Abstract
Aim: Phenylethanolamine N-methyltransferase (PNMT) catalyzes the conversion of sympathetic neurotransmitter norepinephrine to epinephrine. We examined the association of PNMT polymorphisms with acute and chronic pain in sickle cell disease (SCD). Methods: Utilization of emergency care owing to painful crisis was used as a marker for acute pain in 131 patients with SCD. Results: rs876493 A allele, rs2934965 T allele and rs2941523 G allele were significantly associated with decreased utilization (p ≤ 0.05). rs876493 A allele showed association with utilization in females (p = 0.003), not males (p = 0.803). rs2934965 T allele and rs2941523 G allele were predicted to cause loss of putative transcription factor binding sites. This is the first report of the association of PNMT polymorphisms with acute crisis pain in SCD. Together with our previous findings in catechol-o-methyltransferase, polymorphisms in catecholamine metabolizing enzymes appear to primarily influence acute pain in SCD.

PMID: 32162598 [PubMed - as supplied by publisher]